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Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein

Item Type:Article
Title:Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein
Creators Name:Andersen, O.M. and Reiche, J. and Schmidt, V. and Gotthardt, M. and Spoelgen, R. and Behlke, J. and von Arnim, C.A.F. and Breiderhoff, T. and Jansen, P. and Wu, X. and Bales, K.R. and Cappai, R. and Masters, C.L. and Gliemann, J. and Mufson, E.J. and Hyman, B.T. and Paul, S.M. and Nykjaer, A. and Willnow, T.E.
Abstract:sorLA (sorting protein-related receptor) is a type-1 membrane protein of unknown function that is expressed in neurons. Its homology to sorting receptors that shuttle between the plasma membrane, endosomes, and the Golgi suggests a related function in neuronal trafficking processes. Because expression of sorLA is reduced in the brain of patients with Alzheimer's disease (AD), we tested involvement of this receptor in intracellular transport and processing of the amyloid precursor protein (APP) to the amyloid {beta}-peptide (A{beta}), the principal component of senile plaques. We demonstrate that sorLA interacts with APP in vitro and in living cells and that both proteins colocalize in endosomal and Golgi compartments. Overexpression of sorLA in neurons causes redistribution of APP to the Golgi and decreased processing to A{beta}, whereas ablation of sorLA expression in knockout mice results in increased levels of A{beta} in the brain similar to the situation in AD patients. Thus, sorLA acts as a sorting receptor that protects APP from processing into Aβ and thereby reduces the burden of amyloidogenic peptide formation. Consequently, reduced receptor expression in the human brain may increase A{beta} production and plaque formation and promote spontaneous AD.
Keywords:Endocytic receptors, Knockout mouse, Neurodegeneration, Vps10p-domain receptors
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:102
Number:38
Page Range:13461-13466
Date:7 September 2005
Official Publication:https://doi.org/10.1073/pnas.0503689102
PubMed:View item in PubMed

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